PLA2 is an enzyme which hydrolyzes fatty acids from the 2-position of phospholipids. Arachidonic acid (20:4 n-6, AA) is often present in substantial amounts at that position. AA bound to the phospholipid is not pro-inflammatory but once it has been released and is in the free form it can give rise to a wide variety of oxygenated derivatives which are produced by the activities of various enzymes including cyclo-oxygenase and 5-, 12- and 15-lipoxygenases. These derivatives include various prostaglandins, thromboxanes, leukotrienes and other compounds. Many of these AA derivatives play important roles in the promotion of inflammation.
In many circumstances inflammation is an appropriate physiological response to injury and other stimuli. However, all too often it becomes uncontrolled and instead of being beneficial produces both short term and long term damage. Examples of this are the various types of arthritis, of dermatitis, of asthma and of inflammatory bowel disease such as ulcerative colitis, among many others. Drugs which inhibit PLA2, notably the class of glucocorticoids, are usually potent antiinflammatory agents. The natural glucocorticoids and a whole array of synthetic and semi-synthetic derivatives are widely used orally, parenterally and topically on the skin, as aerosols, sprays or other forms of delivery for upper and lower respiratory passages; and as suppositories and other forms of rectally administered products for inflammatory disease of the bowel. However, although these drugs are used so widely they have many side effects and there is a considerable need for appropriate alternatives.